Following a broad panel of immunohistochemical stains, the strong positive staining of the spindle cells for LCA (CD45), CD20, and Bcl-6 confirmed the diagnosis of follicle center cell lymphoma.
The BCL6 transcription factor plays a central role in establishing the GC phenotype in B cells, and most lymphomas are dependent on BCL6 to maintain survival, proliferation, and perhaps immune evasion.
Double/triple-hit lymphomas (DHL/THL) account for 5-10% of diffuse large B cell lymphoma (DLBCL) with rearrangement of MYC and BCL2 and/or BCL6 resulting in MYC overexpression.
Aggressive lymphomas with MYC and BCL2 and/or BCL6 translocations ("double hit" lymphomas, DHL) represent a distinct diagnostic category in the updated World Health Organization (WHO) classification.
We identified 122 patients diagnosed as having large B-cell lymphoma (44, MYC-negative; 29, MYC-EC; 23, MYC rearrangement; 22, MYC and BCL2 rearrangements; 4, MYC, BCL2, and BCL6 rearrangements). p53 expression significantly correlated with DLBCL with abnormal MYC status (MYC-EC, MYC rearrangement, and MYC overexpression), but adverse p53 prognostic effect was only seen with MYC-rearranged lymphoma.
Additionally, CD38<sup>bright</sup> may be a better indicator for predicting DH/THL-BCL2 than DHL-BCL6, and very bright CD38 expression was exclusive to MYC rearranged lymphomas.
High grade B-cell lymphoma (HGBCL) by WHO 2016 classification requires rearrangements of MYC and BCL2 and/or BCL6, practically covering the so called "double-hit" or "triple hit" lymphomas.
Lymphomas with MYC and either BLC2 or BCL6 rearrangements or MYC and BCL-2 protein overexpression, classified as double-hit (DHL) or double-expressor (DEL) lymphomas, respectively, are associated with poorer response to standard immunochemotherapy.
Here we show that the murine lymphoma cell line A20 resembles primary GCB cells in expression of GC-specific surface markers and the master transcription factor BCL6 and may serve as a useful system to model certain GCB cell behaviors in vitro.
Simple karyotyping revealed key translocations involving MYC, BCL2, and BCL6 that have impacted lymphoma classification in the World Health Organization classification scheme.
Lymphomas with pseudo-double-hit BCL6-MYC translocations due to t(3;8)(q27;q24) are associated with a germinal center immunophenotype, extranodal involvement, and frequent BCL2 translocations.
High-grade B-cell lymphomas (HGBLs) with MYC and BCL2 and/or BCL6 rearrangements, so-called "double-hit" lymphomas (HGBL-DH), are aggressive lymphomas that form a separate provisional entity in the 2016 revised World Health Organization Classification of Lymphoid Tumors.
Therefore, identification of the normal B cell subset with the most similar gene expression pattern to a particular type of B cell lymphoma has been instrumental to deduce the precise cell of origin of lymphomas.We present here protocols to analyze human B cell lymphomas for a potential origin from GC B cells by determining the presence of mutations in rearranged IgV genes and the BCL6 gene, and by comparing the gene expression pattern of lymphoma cells with those of normal B cell subsets by genechip or RNA-sequencing analysis.
In this review, we summarize two sessions dedicated to "high-grade B cell lymphomas, with MYC and BCL2 and/or BCL6 rearrangements (so-called double/triple-hit lymphomas)" and "high-grade B cell lymphomas, NOS" as defined in the 2016 update of the WHO lymphoma classification, Burkitt lymphoma and related neoplasms, and terminally differentiated aggressive B cell lymphomas.
There were 47 DTHLs, 36 cases with MYC and BCL2 and/or BCL6 extra signals (ES) and/or rearrangements (ES group, excludes DTHLs), 9 with MYC rearrangements only (single-hit lymphoma), and 95 with no MYC abnormalities (NM).
We demonstrate the usefulness of synthetic lethal screening of a conditionally BCL6-deficient Burkitt lymphoma cell line, DG75-AB7, with a library of small molecules to determine survival pathways suppressed by BCL6 and suggest mechanism-based treatments for lymphoma.